9-83504130-G-T

Position:

• chr9-83504130-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174938.6(FRMD3):​c.147+33955C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,830 control chromosomes in the GnomAD database, including 13,871 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13871 hom., cov: 31)
• Consequence: FRMD3 NM_174938.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

Genes affected

FRMD3 (HGNC:24125): (FERM domain containing 3) The protein encoded by this gene is a single pass membrane protein primarily found in ovaries. A similar protein in erythrocytes helps determine the shape of red blood cells, but the function of the encoded protein has not been determined. There is some evidence that this is a tumor suppressor gene, and there is also evidence linking defects in this gene to susceptibility to diabetic nephropathy in type 1 diabetes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMD3	NM_174938.6	c.147+33955C>A		intron_variant		ENST00000304195.8	NP_777598.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMD3	ENST00000304195.8	c.147+33955C>A		intron_variant		1	NM_174938.6	ENSP00000303508	P1
FRMD3	ENST00000376438.5	c.147+33955C>A		intron_variant		2		ENSP00000365621

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62532 AN: 151712 Hom.: 13866 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.448

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.412 AC: 62551 AN: 151830 Hom.: 13871 Cov.: 31 AF XY: 0.409 AC XY: 30350 AN XY: 74200

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.448

Alfa AF: 0.482 Hom.: 9759

Bravo AF: 0.410

Asia WGS AF: 0.426 AC: 1485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.72
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4877785; hg19: chr9-86119045;